US8053188B2 - Nucleic acid enrichment - Google Patents

Nucleic acid enrichment Download PDF

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US8053188B2
US8053188B2 US10/495,895 US49589504A US8053188B2 US 8053188 B2 US8053188 B2 US 8053188B2 US 49589504 A US49589504 A US 49589504A US 8053188 B2 US8053188 B2 US 8053188B2
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nucleic acid
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hybridized
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Mats Gullberg
Ulf Landegren
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Landegren Gene Technology AB
Olink Holding AB
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813—Hybridisation assays
    • C12Q1/6827—Hybridisation assays for detection of mutation or polymorphism
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6844—Nucleic acid amplification reactions
    • C12Q1/6858—Allele-specific amplification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813—Hybridisation assays
    • C12Q1/6827—Hybridisation assays for detection of mutation or polymorphism
    • C12Q1/683—Hybridisation assays for detection of mutation or polymorphism involving restriction enzymes, e.g. restriction fragment length polymorphism [RFLP]

Definitions

  • This invention relates to methods, reagents and kits for enriching nucleic acid sequences. More particularly, the present invention relates to methods, reagents and kits for sample preparation including sample modification, sample enrichment and amplification.
  • Haplotype information can be vital in the analysis of disease by determining whether two or more sequence variants are located on the same nucleic acid fragment. This is of special interest in tumour research and diagnosis where it is important to know if two or more inactivating mutations occur on the same or different chromosomes. Similarly better information about which genotypes are located on the same nucleic acid segment can greatly increase the information derived from genotyping data and in the statistical analysis of genetic linkage or linkage disequilibrium of inherited traits and markers such as single nucleotide polymorphisms, SNPs (e.g. [1-3]).
  • SNPs single nucleotide polymorphisms
  • haplotyping is important to be able to relate genetic factors to a patient's response to various drugs, [4].
  • haplotype information can also be gained from hemizygous X- and Y-chromosomes, where haplotypes are immediately apparent from the genotype.
  • the possibility to study cells with only one autosome chromosome is utilised in some in vivo techniques.
  • One approach is the creation of rodent-human hybrid cells, for example using the so called “Conversion technology” [2]. Some of the rodent-human hybrid cells will contain one of the two possible copies from a human chromosome.
  • a second approach is to use hydatidiform moles, i.e. tissues that due to a fertilisation defect only contain genetic material from the sperm (complete hydatidiform mole) thereby containing only one copy of each chromosome.
  • haplotypes There are also some in vitro molecular techniques that can be used to determine haplotypes.
  • One technique is the sub-cloning of all nucleic acid sequences of interest, isolating individual clones and subsequently genotyping them. Allele-specific analysis through Fibre Fluorescent In Situ Hybridisation is another possible approach, however it has not yet been convincingly shown to be useful for SNP based haplotyping.
  • a third approach is double PCR Allele Specific Amplification (double-PASA [5], a double allele-specific Polymerase Chain Reaction (PCR) which gives linkage information of two adjacent polymorphic sites. Pyrosequencing [6] and mass spectrometry may be used to analyse haplotypes over short distances, i.e. ⁇ 100 nt.
  • a general technique is provided to obtain haplotypes through enrichment for one nucleic acid segment to include a specific variant at a given position. Thereby any variant position in a sample could be used for selection, followed by analysing genetic variants elsewhere in the same nucleic acid fragment.
  • the same principle can be used for genotyping or to generate probes that reveal the genotype at particular loci.
  • the present invention provides a method for sample preparation that optionally includes the steps of: (a) cleavage of a nucleic acid so that a fragment containing the sequence to be investigated is created with or without addition of oligonucleotide probes (b) selective modification of one variant of the nucleic acid sequences (c) enrichment of the selected variant, and (d) analysis of the nucleic acid.
  • the present invention also provides one or several probes for use in the described methods.
  • a first set of probes/probe preferably directs site specific cleavage at predetermined sites of the sample upon hybridisation.
  • a second set of probes/probe is used to specifically modify the sample based upon the presence or absence of a given sequence variant.
  • a third set of probes is used for amplification of the sample and a fourth set of probes is used for scoring the genotypes.
  • the present invention describes several ways to enrich a nucleic acid sequence or sequences from a multitude of sequences on the basis of the sequence or on the basis of a particular sequence variation at a given position.
  • nucleic acid refers to any combination of nucleotides, covalently linked as such to form linear molecules of DNA or RNA.
  • variant describes interchangeably and without preference a nucleic acid encoding a variant, which may for example be selected from the group including any one or more of the following; a single nucleotide sequence variant, deletion sequence variant, insertion sequence variant, sequence length variants, and sequence variation among paralogous or orthologous nucleic acid sequence, or among edited sequences or splice variants
  • the first approach is based on cleavage of DNA at any predetermined site through the use of so called nucleic acid adapters, hereafter called adapters, that are targets or part of targets for restriction enzymes preferably type II or type IIs restriction enzymes [7,8].
  • Adapters and sample are mixed, denatured and subsequently allowed to cool.
  • the adapters hybridise to their complementary regions in the sample nucleic acid.
  • One of the adapters is positioned so that the resulting cleaved sample DNA contains a variant position at the 5′ position (A).
  • Added restriction enzymes cleave the sample and, through addition of a ligation template that anneals to both the 5′ and 3′ end of the cleaved sample DNA, circular molecules are obtained by ligation of the ends that are brought next to each other (B). This circularisation is driven by the higher relative concentration of two ends belonging to the same molecule compared to those of two different copies of the same or similar molecules. If the added template is complementary to the sample DNA-ends, juxtaposing these, then ligation of the two ends can occur. If a mismatch between the sample DNA and the ligation template exists at the variant position used for selection, or if there are no free ends at the site intended for ligation, then ligation will not occur. Circularised molecules can then be enriched for through the use of exonucleases that degrade uncircularised DNA, and/or amplification of the circularised DNA, for example with rolling circle amplification (RCA) can be performed ([9,10]).
  • RCA rolling circle amplification
  • the adapter could be positioned upstream of the variant position used for selection.
  • this adapter could be completely omitted.
  • template one or a plurality of oligonucleotides is added, (template), which hybridises to both the 3′ end and to an upstream sequence around the variant position, as shown in FIG. 2A .
  • This provides a specificity step.
  • the structure is then cleaved by chemical, enzyme or other means to generate a structure, as shown in FIG. 2B . Where an enzyme is used, any enzyme capable of cleaving such a structure may be used [11].
  • the enzyme is preferably selected from, FEN nuclease, Mja nuclease, native or recombinant polymerase from Thermus aquatiqus, Thermus thermophilus , or Thermus flavus , or any enzyme selected according to the teachings of Lyamichev et al [11] or U.S. Pat. No. 5,846,717, which are incorporated herein by reference.
  • the variant position used for selection can either be removed by cleavage, or the cleavage can be performed so that the variant position is the 5′-most nucleotide of the sequence. Hence the major selective step is in the subsequent ligation reaction.
  • nucleic acid ligation for allele distinction is well described in the literature, for example [12,13].
  • 3′ sample nucleotide must be complementary to the added template. This can be achieved directly from cleavage of the sample, in which case it is possible to ligate the DNA directly.
  • Another approach which confers increased specificity, is to construct the added template so that it contains one extra nucleotide, giving a gap between the hybridised 3′ and 5′ sequences, similar to that observed for the SNP.
  • a substrate for cleavage will only be generated from nucleic acid sequences that contain the complementary nucleic acid sequence.
  • This gap may be filled in by the addition of a complementary oligonucleotide, as shown in FIG. 2C .
  • this gap filling oligonucleotide can be labelled with an affinity tag, for example a specific sequence or specific molecule for subsequent affinity purification.
  • the gap filling oligonucleotide can also be of a specific sequence to be used for circular DNA amplification as described in co-pending application PCT/SE02/01378.
  • Cleavage of the sample DNA can also be achieved with restriction enzymes through the addition of oligonucleotides that hybridise to the selected sequence.
  • the 5′ cleavage site may or may not be influenced by the variable sequence. Circularisation and selection is then conducted via any of the above-mentioned approaches.
  • the nucleic acid fragment ends can be protected via addition of protecting adapters to one or both ends based on selective addition at a variant position at at least one of the ends, as shown in FIG. 3 .
  • Generation of the 3′ or 5′ sample ends could be achieved either through cleavage at the variable position or upstream at a generic site, as previously described. In the latter case cleavage will be performed via structure-specific cleavage as previously described.
  • This protected linear substrate can now be enriched for, through degradation of unprotected sample using exonucleases. Selective amplification of the protected allele can be performed based on the presence of the added sequence/sequences.
  • restriction enzymes having recognition sequences located on either side but not within the sequence of interest, can be used.
  • Double stranded DNA can be digested at a multitude of sites with one or several different restriction enzymes. Digestion at one or several of the sites may or may not be affected by a sequence variant. If one specific sequence variant affects digestion by a restriction enzyme at a given site, only one of the alleles will become circularised upon ligation with a ligation template in the form a ligation casette.
  • a ligation cassette consists of a pair of prehybridized complementary oligonucleotides with single stranded sequences protruding at one or both ends to form a correct ligation site for the chosen sequences to be ligated. Only the circularised allele becomes a template for circular amplification by e.g. rolling circle amplification.
  • the RCA amplified allele will be the only single stranded DNA in the sample.
  • This single stranded DNA can then be genotpyed by a single strand specific genotyping method such as, including by way of example only, padlock probes, oligonucleotide ligation assay or invader assay.
  • the principle of specifically generate only a subset of a sample single stranded can be utilized with any method capable of performing such an action and is not to be limited to the one mentioned. Subsequent analysis with single strand specific methods reveals the genotype of only the selected, and thus single stranded sequence.
  • an exonuclease is added to make one or both ends of a restriction enzyme digested double stranded sample partially single stranded before circularization.
  • a chosen specific sequence is circularized, templated by an added oligonucleotide or pairs of oligonucleotides either directly or via a structure-specific enzyme cut, as described above, followed by specific ligation.
  • the strands are then gap-filled, followed by DNA ligation. Only the correct allele can be made into a complete circle possible to amplify with RCA.
  • a further variant to generate single stranded DNA from a restriction enzyme digested of a double stranded sample is to specifically degrade only one of the strands with exonucleases. This can be achieved, by way of example only, through making a proper choice of restriction enzymes that will produce a sticky end that is not a substrate for the chosen exonuclease or exonucleases; or via DNA ligation adding a protecting sequence to one or both of the ends; or via DNA ligation add a chemically modified and protected sequence to one or both of the ends.
  • the single stranded DNA can then be circularized, either directly via specific ligation or via a structure-specific enzyme cut followed by specific ligation as previously described.
  • a second generation RCA is conducted, primed with a second oligonucleotide, effectively amplifying only the circularised allele.
  • the enriched sample can be subjected to genotyping through any method and compared to results from genotyping of the total sample.
  • methods which may be used are oligonucleotide ligation assays [12], padlock probes [13], primer extension assays [14], pyrosequencing [15], invader technology[16], mass-spectroscopy [17] or homogenous PCR methods e.g. Taqman [18] or molecular beacons [19].
  • other methods may be employed with equal utility.
  • the enriched sample instead of a whole sample as the test sample it is also feasible to use any suitable method-, to find new/unknown mutations or polymorphisms.
  • all possible mutations in the enriched segment may be detected, also unknown ones, for example by Sanger sequencing or by hybridising the enriched sample to an array in order to resequence the sample and in this respect also find new or unknown mutations.
  • the methods could be, but are not limited to the use of, mismatch recognising enzymes for example T4 endo VII [20], DHPLC resequencing, Sanger or array, or pyrosequencing [15]. However, other methods may be employed with equal utility.
  • the resulting genotypes will reveal the specific haplotype of the sample.
  • the present invention provides one or several sets of probes.
  • a first set of probes/probe direct site specific cleavage at predetermined sites of the sample upon hybridisation.
  • a second set of probes/probe is used to specifically modify the sample based upon a sequence variant.
  • a third set of probes is used for amplification of the sample and a fourth set of probes is used for scoring the genotypes.
  • an oligonucleotide can be added that anneals to the 3′ end of a generated fragment and to a stretch upstream, around the variant position to be scored, so that a probe with a hybridising region at its 5′ end is formed, (as shown in FIG. 4A ), or a probe with a non-hybridising region at its 5′ end is formed, (as shown in FIG. 4B ). If necessary this structure can then be cleaved as previously described. The use of ligase will complete the nucleic acid circle.
  • the circle can then be enriched for, using exonuclease treatment and nucleic acid amplification, preferably rolling circle amplification.
  • the oligonucleotide added contains a sequence between the 3′ and the 5′ hybridising end that consist of a selected sequence used for later hybridisation that can be rendered double stranded through the addition of a second oligonucleotide, shown in FIG. 4A as object 1 .
  • the added oligonucleotide could contain a recognition sequence for a type IIs restriction enzyme and preferably a sequence as dissimilar as possible compared to other oligonucleotides used for other loci, as described in co-pending application PCT/SE02/01378, the contents of which are incorporated herein by reference. Detection of the circularised nucleic acid or amplification products templated by the circularised nucleic acid is used to score the genotype of the selected position.
  • the present invention further provides one or a set of probes.
  • a first set of probes/probe directs site-specific cleavage at predetermined sites of the sample upon hybridisation.
  • a second set of probes/probe is used to specifically modify the sample based upon a sequence variant.
  • a third set of probes is used for amplification of the enriched sample.
  • the variant position could be, but is not limited to a sequence variant polymorphism which may be selected from the group including any one or more; deletion variant, insertion variant, sequence length variant, single nucleotide polymorphism, substitution variant, paralogous or orthologous nucleic acid sequences, edited sequences or splice variants.
  • the present invention is also to be used as a mean to isolate and enrich for a specific sequence or sequences among a multitude of sequences, with the intention of further manipulation of the enriched sequence/sequences.
  • the methods could be any, sole or a combination of but not limited to, amplification, quantification, sequencing, variant scoring, using the enriched sequence/sequences as probes or to compare different enriched samples on the basis of for example amount of sample.
  • the present invention further provides one or a set of probes.
  • a first set of probes/probe directs site specific cleavage at predetermined sites of the sample upon hybridisation.
  • a second set of probes/probe is used to specifically modify the sample based upon a nucleotide sequence.
  • a third set of probes is used for amplification of the enriched sample.
  • An added oligonucleotide probe can also be treated by the same principles and to be used for subsequent genotyping, as shown in FIG. 5 , if the added oligonucleotide anneals forming a non-hybridising region at the 5′ end. Cleavage of this structure will generate a molecule that can be circularised with a ligase. Ligation will depend on whether the 5′ nucleotide is matched or not with the sample. This circularised probe can then be detected either directly or via the presence of amplification products (based on the presence of the circle or amplification products of the circle). The presence of such a product describes the nature of the variant position.
  • the added oligonucleotide could preferentially contain a molecule or sequence in the 5′ part that is used as an affinity tag for removal of unmodified circles before amplification of the circularised probes.
  • the present invention provides one or a set of probes.
  • a second set of probes could be used for purification of the sample.
  • a third set of probes is used for amplification of the modified probes.
  • FIG. 1 is a schematic representation of cleavage and circularisation of sample nucleic acid through the use of adapters
  • FIG. 2 is a schematic representation of structure specific cleavage for circularisation of sample nucleic acids
  • FIG. 3 is a schematic representation of addition of protecting ends to a linear nucleic acid sample
  • FIG. 4 is a schematic representation of the use of gap-oligonucleotides for circularisation of sample nucleic acids
  • FIG. 5 is a schematic representation of scoring SNPs through circularisation of nucleic acid probes
  • FIG. 6 shows (A) the result from a real-time PCR experiment and (B) the gel of the same amplification reactions from an experiment of cleaving, ligating and rolling circle amplification of BAC DNA;
  • FIG. 7 is a schematic representation (A) of the experimental set-up for detection of circularisation of nucleic acids via inverse PCR and (B) a photo of an agarose gel showing the result of such an experiment where BAC DNA cut with FokI adapters, circularised with ligase, circular molecules enriched for via exonucleases and finally used for template in an inverse PCR reaction;
  • FIG. 8 is showing an image of a poly acrylamide gel of radioactive labelled nucleic acids showing cleavage and ligation of structure specific cleaved nucleic acids with native DNA Taq polymerase and Tth ligase;
  • FIG. 9 is showing a photo of an ethidium bromide stained gel of amplification products obtained from an experiment with cleaved BAC DNA that had been circularised via cleavage by a structure specific enzyme and the two ends joined by a ligase.
  • Circularisation of DNA after cleavage with restriction enzymes followed by enrichment through exonuclease treatment and rolling circle amplification See FIG. 4 .
  • a BAC clone (RP11-381L18, BacPac resources, Children's hospital, Oakland) with a genomic fragment containing the gene ATP7B was used. DNA was isolated by the rapid alkaline lysis miniprep method and the DNA concentration was determined measuring UV A 260 .
  • HpaII 5 U (New England Biolabs) was used to cleave a double stranded (ds) template in buffer (10 mM Tris-HCl pH 7.5, 10 mM MgCl 2 , 1 mM DTT) for 2 hours at 37° C. before heat-inactivation of the enzyme. Two pmol of the ds template was cleaved with HpaII. After the cleavage, the reaction was diluted to different concentrations (10 4 -10 8 molecules/ ⁇ l).
  • the template was ligated into a circle using 0.5 units of T4 DNA ligase, 1 ⁇ T4 DNA ligase bf (66 mM Tris-HCl pH 7.6, 6.6 mM MgCl 2 , 10 mM DTT, 66 ⁇ M ATP) and 10 nM ligation template, 5′Biotin-tt ttt ttt ttt tttt gtc tgg aaa gca aac cgg tgc cca ccc atg a 3′ SEQ ID NO1, in each reaction. After denaturation and subsequent addition of ligase to half of the reactions (see below), the samples were incubated at 37° C. for 30 min and then the ligase was heat-inactivated at 65° C. for 20 minutes
  • Exonuclease V 5 units was used for 30 min 37° C. before heat-inactivation. The result was detected by performing a PCR with the following primers, 5 acg ccc acg gct gtc at 3′ SEQ ID NO2 and 5′ tgg acg tct gga aag caa a 3′ SEQ ID NO3, (1 ⁇ M) located on both sides of the ligation junction.
  • FIG. 4 The results are shown in FIG. 4 , where A) Graph showing the fluorescence readings from a real-time PCR experiment read in an ABI 7700. The figures to the left corresponds to the numberings in B. Reactions were as follows; #2, 3—No template control, #4 sample+ligase, #5 Sample ⁇ ligase, #6 sample+ligase+RCA, #7 Sample ⁇ ligase+RCA
  • Lane 1 in B is loaded with a 100 bp-ladder (lowest band around 50 bp).
  • Lane 2-7 corresponds to the same reactions.
  • the arrow denotes the size for a correct length product.
  • BAC DNA as described in example 1 were cleaved and ligated as described in EXAMPLE 1. Half of the sample was ligated with T4 DNA ligase and half of the sample was not. The two reactions were further divided into five different reactions of each (+/ ⁇ ligase) treated as follows.
  • BAC DNA was purified as described in example 1.
  • BAC DNA was diluted in a series and denatured by heat. After denaturation the samples were directly put on ice.
  • FokI and 2 fmol FokI adapters (FokI adapter 5′UTR 5′ cgc atc cca cgt ggg atg cga aag caa aca ggg gt 3′ SEQ ID NO4, FokI adapter C2930T C-allele 5′ gcc atc cgt gca cgg atg gct gca cag cac cgt gat 3′ SEQ ID NO5, FokI adapter C2930T T-allele 5′ gcc atc cgt gca cgg atg gct gca cag cac cat gat 3′ SEQ ID NO6) in 10 mM Tris-HCl pH 7.5, 10 mM MgCl 2 , 1 mM DTT, 50 mM NaCl, 1 ⁇ BSA1 for 2 hours 37° C. before heat
  • the ends of the generated fragment nucleic acid were ligated into a circle using 8 fmol of the correct/incorrect ligation template (20+20 WDgDNA 5′UTR-Ex13 C-allele, 5′ ctc ggc tct aaa gca aac agg tga tgg acg tct gga aag ctt t 3′ SEQ ID NO7, 20+20 WDgDNA 5′UTR-Ex13 T-allele 5′ ctc ggc tct aaa gca aac aga tga tgg acg tct gga aag cttt t 3′ SEQ ID NO8).
  • T4 DNA ligase and 1 ⁇ T4 DNA ligase buffer was used, and the reactions were incubated for approximately 30 minutes at 37° C. before heat-inactivation of the DNA ligase.
  • the circles were exonuclease treated with 5 units ExoV and 1 mM ATP and the samples were incubated in 37° C. for 30 min before heat-inactivation at 80° C. for 20 minutes.
  • PCR amplification was performed with primers (Frw WDgDNA 5′UTR-Ex13 5′ cag agg tga tca tcc ggt ttg 3′ SEQ ID NO9, Rew WDgDNA 5′UTR-Ex13 5′ gga gag gag gcg cag agt gt 3′ SEQ ID NO10), 0.5 ⁇ M of each, located on both sides of the ligation junction.
  • the results are shown in FIG. 6B .
  • the following samples were loaded into the different lanes; 1—Marker, 2 No template control, 3-8 samples from a 10-fold dilution series (10 10 -10 1 ) of BAC DNA with correct ligation template and ligase, 9 sample with correct ligation template but minus ligase, 10-12 samples from a 10-fold dilution series (10e10 to 10e9) with a ligation template corresponding to the wrong allele, T instead of C).
  • the arrow denotes the size of a correct length product.
  • the reactions were prepared on ice and initiated by transfer to a Thermal Cycle where the following program was run: 95° C. 20 sec, 72° C. 30 min for 2 cycles.
  • the upstream or downstream oligonucleotide was radio labelled and the samples were analysed on a 10% denaturing polyacrylamide gel.
  • Ten pmol target DNA was end-labelled with 1.65 pmol ⁇ - 32 P dATP (NEN).
  • 4.9 U T4 PNK enzyme and 1 ⁇ T4 PNK buffer (0.05 M Tris-HCl pH 7.6, 10 mM MgCl 2 , 10 mM 2-mercaptoethanol) was added to each labelling reaction and the tubes were incubated for 45 min in 37° C.
  • EDTA (1 mM) was added and the samples were boiled for 5 min in a water bath.
  • the unincorporated nucleotides were removed from the labelling reaction with a MicroSpinTM G-50 column (Amersham Pharmacia Biotech).
  • Oligonucleotides yielding structure A was used in experiments 1-6 and oligonucleotides yielding structure B was used in experiments 7-12.
  • 32P denotes a radioactive label on respective oligonucleotide.
  • Lanes 1-6 shows the results from experiments with oligonucleotide 1 labelled with 32 P.
  • Lane 1 T-allel (wrong)—Taq polymerase, lane 2 C-allel (correct)—Taq polymerase, lane 3 T-allele—Tth ligase, lane 4 C-allel—Tth ligase, lane 5 T-allel, lane 6 C-allele.
  • Lanes 7-12 show the results from experiments with oligonucleotide 2 radio labelled with P 32 Lanes 7, 9, 11 is with the T-allele (incorrect) and lane 8, 10, 12 is with the C-allele (correct). Lanes 7-8 minus Taq polymerase, lanes 9-10 minus Tth ligase.
  • Lane 13 shows size markers.
  • BAC DNA was purified as described in example 1.
  • DraIII Denatured, ss BAC DNA (1 ⁇ 10 10 molecules) was cleaved with 10 units DraIII in buffer (10 mM NaCl, 5 mM Tris-HCl, 1 mM MgCl 2 , 0.1 mM DTT pH 7.9) was used. DraIII was allowed to cleave the DNA for 1 hour 37° C. before heat-inactivation.
  • the subsequent concerted structure-specific cleavage and ligation reaction contained the same reagents as above and 2 pmol of ligation any of two different templates (20+20 DraIII-C 5′ taa acg acc cgt gag tga cgc aca ggt cac ggg ggg ac 3′ SEQ ID NO17 or 20+20 DraIII-G 5′ taa acg acc cgt gag tga cgg aca ggt cac ggg ggg ac 3′ SEQ ID NO18).
  • the samples were divided into two parts and on one half was subjected to a RCA.
  • a real-time PCR was performed on the samples with primers located on both sides of the ligation junction.
  • the following reagents were included: 2.5 ⁇ l sample, 1 ⁇ PCR bf, 100 ⁇ M dNTP, 1 unit Taq GOLD polymerase, 0.5 ⁇ M of each primer, 1 ⁇ ROX and 0.08 ⁇ SYBR.
  • DraIII and specific adapters designed to hybridise to sequences in exon 13 of ATP7B cleaved BAC DNA at predetermined sites The target DNA was denatured to become single-stranded and the adapters were designed to create recognition and cleavage sites for DraIII.
  • DraIII cleavage created a substrate that was used in the structure-specific cleavage, which generated the 5′ located SNP.
  • FIG. 8 Shown is the samples run on a 3% agarose gel. Lane 1 is a size marker, lane 2 and 3 PCR no template controls, lane 4 sample, lane 5 without Taq polymerase, lane 6 without Tth ligase and lane 7 without BAC DNA.

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013090469A1 (en) 2011-12-13 2013-06-20 Sequenta, Inc. Detection and measurement of tissue-infiltrating lymphocytes
WO2015002908A1 (en) 2013-07-01 2015-01-08 Sequenta, Inc. Large-scale biomolecular analysis with sequence tags
US9150905B2 (en) 2012-05-08 2015-10-06 Adaptive Biotechnologies Corporation Compositions and method for measuring and calibrating amplification bias in multiplexed PCR reactions
US9181590B2 (en) 2011-10-21 2015-11-10 Adaptive Biotechnologies Corporation Quantification of adaptive immune cell genomes in a complex mixture of cells
US9279146B2 (en) 2012-12-21 2016-03-08 Roche Molecular Systems, Inc. Compounds and methods for the enrichment of mutated nucleic acid from a mixture
US9347099B2 (en) 2008-11-07 2016-05-24 Adaptive Biotechnologies Corp. Single cell analysis by polymerase cycling assembly
US9365901B2 (en) 2008-11-07 2016-06-14 Adaptive Biotechnologies Corp. Monitoring immunoglobulin heavy chain evolution in B-cell acute lymphoblastic leukemia
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US9512487B2 (en) 2008-11-07 2016-12-06 Adaptive Biotechnologies Corp. Monitoring health and disease status using clonotype profiles
US9518290B2 (en) 2013-09-10 2016-12-13 Samsung Electronics Co., Ltd. Method for detecting nucleic acids by amplification of a circularized nucleic acid
US9528160B2 (en) 2008-11-07 2016-12-27 Adaptive Biotechnolgies Corp. Rare clonotypes and uses thereof
US9618510B2 (en) 2013-03-13 2017-04-11 Meso Scale Technologies, Llc. Assay methods
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US9824179B2 (en) 2011-12-09 2017-11-21 Adaptive Biotechnologies Corp. Diagnosis of lymphoid malignancies and minimal residual disease detection
US9873908B2 (en) 2013-11-27 2018-01-23 Roche Molecular Systems, Inc. Methods for the enrichment of mutated nucleic acid from a mixture
US10066265B2 (en) 2014-04-01 2018-09-04 Adaptive Biotechnologies Corp. Determining antigen-specific t-cells
US10077478B2 (en) 2012-03-05 2018-09-18 Adaptive Biotechnologies Corp. Determining paired immune receptor chains from frequency matched subunits
US10114015B2 (en) 2013-03-13 2018-10-30 Meso Scale Technologies, Llc. Assay methods
US10112194B2 (en) 2014-04-14 2018-10-30 Q-Linea Ab Detection of microscopic objects
US10150996B2 (en) 2012-10-19 2018-12-11 Adaptive Biotechnologies Corp. Quantification of adaptive immune cell genomes in a complex mixture of cells
US10221461B2 (en) 2012-10-01 2019-03-05 Adaptive Biotechnologies Corp. Immunocompetence assessment by adaptive immune receptor diversity and clonality characterization
US10227632B2 (en) 2013-11-29 2019-03-12 Q-Linea Ab Rolling circle amplification method
US10246701B2 (en) 2014-11-14 2019-04-02 Adaptive Biotechnologies Corp. Multiplexed digital quantitation of rearranged lymphoid receptors in a complex mixture
US10323276B2 (en) 2009-01-15 2019-06-18 Adaptive Biotechnologies Corporation Adaptive immunity profiling and methods for generation of monoclonal antibodies
US10385475B2 (en) 2011-09-12 2019-08-20 Adaptive Biotechnologies Corp. Random array sequencing of low-complexity libraries
US10392663B2 (en) 2014-10-29 2019-08-27 Adaptive Biotechnologies Corp. Highly-multiplexed simultaneous detection of nucleic acids encoding paired adaptive immune receptor heterodimers from a large number of samples
US10428325B1 (en) 2016-09-21 2019-10-01 Adaptive Biotechnologies Corporation Identification of antigen-specific B cell receptors
US11041202B2 (en) 2015-04-01 2021-06-22 Adaptive Biotechnologies Corporation Method of identifying human compatible T cell receptors specific for an antigenic target
US11047008B2 (en) 2015-02-24 2021-06-29 Adaptive Biotechnologies Corporation Methods for diagnosing infectious disease and determining HLA status using immune repertoire sequencing
US11066705B2 (en) 2014-11-25 2021-07-20 Adaptive Biotechnologies Corporation Characterization of adaptive immune response to vaccination or infection using immune repertoire sequencing
US11248253B2 (en) 2014-03-05 2022-02-15 Adaptive Biotechnologies Corporation Methods using randomer-containing synthetic molecules
US11254980B1 (en) 2017-11-29 2022-02-22 Adaptive Biotechnologies Corporation Methods of profiling targeted polynucleotides while mitigating sequencing depth requirements
US11525825B2 (en) 2014-05-15 2022-12-13 Meso Scale Technologies, Llc. Assay kits
US11597965B2 (en) 2017-10-06 2023-03-07 10X Genomics, Inc. RNA templated ligation
US12105084B2 (en) 2019-12-03 2024-10-01 Alamar Biosciences, Inc. Nucleic acid linked immune-sandwich assay (NULISA)
US12534751B1 (en) 2020-03-27 2026-01-27 Olink Proteomics Ab Products for protein analyte detection assays using antibodies
US12553887B2 (en) 2019-03-01 2026-02-17 Meso Scale Technologies, Llc. Electrochemiluminescent labeled probes for use in immunoassay methods, methods using such and kits comprising same

Families Citing this family (56)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4691014B2 (ja) * 2003-02-26 2011-06-01 カリダ ゲノミクス，インコーポレーテッド ハイブリダイゼーションによるランダムアレイｄｎａ分析
SE0401270D0 (sv) 2004-05-18 2004-05-18 Fredrik Dahl Method for amplifying specific nucleic acids in parallel
EP3257949A1 (de) 2005-06-15 2017-12-20 Complete Genomics Inc. Nukleinsäureanalyse durch zufällige mischungen von nichtüberlappenden fragmenten
US20090264299A1 (en) 2006-02-24 2009-10-22 Complete Genomics, Inc. High throughput genome sequencing on DNA arrays
CA2624896C (en) 2005-10-07 2017-11-07 Callida Genomics, Inc. Self-assembled single molecule arrays and uses thereof
US7960104B2 (en) * 2005-10-07 2011-06-14 Callida Genomics, Inc. Self-assembled single molecule arrays and uses thereof
US8137936B2 (en) * 2005-11-29 2012-03-20 Macevicz Stephen C Selected amplification of polynucleotides
US20070168197A1 (en) * 2006-01-18 2007-07-19 Nokia Corporation Audio coding
US8460879B2 (en) 2006-02-21 2013-06-11 The Trustees Of Tufts College Methods and arrays for target analyte detection and determination of target analyte concentration in solution
EP2495337A1 (de) 2006-02-24 2012-09-05 Callida Genomics, Inc. Genomsequenzierung auf DNA-Arrays mit hohem Durchsatz
WO2008070352A2 (en) 2006-10-27 2008-06-12 Complete Genomics, Inc. Efficient arrays of amplified polynucleotides
US20090111706A1 (en) 2006-11-09 2009-04-30 Complete Genomics, Inc. Selection of dna adaptor orientation by amplification
US20080221832A1 (en) * 2006-11-09 2008-09-11 Complete Genomics, Inc. Methods for computing positional base probabilities using experminentals base value distributions
US7862999B2 (en) 2007-01-17 2011-01-04 Affymetrix, Inc. Multiplex targeted amplification using flap nuclease
WO2008118679A1 (en) * 2007-03-23 2008-10-02 Ge Healthcare Bio-Sciences Corp. Multiply-primed amplification of circular nucleic acid sequences
US20080293589A1 (en) * 2007-05-24 2008-11-27 Affymetrix, Inc. Multiplex locus specific amplification
US9388457B2 (en) 2007-09-14 2016-07-12 Affymetrix, Inc. Locus specific amplification using array probes
US8716190B2 (en) 2007-09-14 2014-05-06 Affymetrix, Inc. Amplification and analysis of selected targets on solid supports
WO2009052214A2 (en) * 2007-10-15 2009-04-23 Complete Genomics, Inc. Sequence analysis using decorated nucleic acids
US7897344B2 (en) * 2007-11-06 2011-03-01 Complete Genomics, Inc. Methods and oligonucleotide designs for insertion of multiple adaptors into library constructs
US7901890B2 (en) * 2007-11-05 2011-03-08 Complete Genomics, Inc. Methods and oligonucleotide designs for insertion of multiple adaptors employing selective methylation
US8298768B2 (en) * 2007-11-29 2012-10-30 Complete Genomics, Inc. Efficient shotgun sequencing methods
US8518640B2 (en) * 2007-10-29 2013-08-27 Complete Genomics, Inc. Nucleic acid sequencing and process
US20090263872A1 (en) * 2008-01-23 2009-10-22 Complete Genomics Inc. Methods and compositions for preventing bias in amplification and sequencing reactions
US8415099B2 (en) * 2007-11-05 2013-04-09 Complete Genomics, Inc. Efficient base determination in sequencing reactions
US8592150B2 (en) 2007-12-05 2013-11-26 Complete Genomics, Inc. Methods and compositions for long fragment read sequencing
WO2009097368A2 (en) 2008-01-28 2009-08-06 Complete Genomics, Inc. Methods and compositions for efficient base calling in sequencing reactions
US20090233809A1 (en) * 2008-03-04 2009-09-17 Affymetrix, Inc. Resequencing methods for identification of sequence variants
US20090270273A1 (en) * 2008-04-21 2009-10-29 Complete Genomics, Inc. Array structures for nucleic acid detection
US20100112556A1 (en) * 2008-11-03 2010-05-06 Sampson Jeffrey R Method for sample analysis using q probes
US8691510B2 (en) 2008-11-07 2014-04-08 Sequenta, Inc. Sequence analysis of complex amplicons
US9524369B2 (en) 2009-06-15 2016-12-20 Complete Genomics, Inc. Processing and analysis of complex nucleic acid sequence data
EP2542890B1 (de) 2010-03-01 2015-05-06 Quanterix Corporation Verfahren zur erweiterung des dynamischen bereichs bei tests für den nachweis von molekülen oder partikeln
US8236574B2 (en) 2010-03-01 2012-08-07 Quanterix Corporation Ultra-sensitive detection of molecules or particles using beads or other capture objects
US9952237B2 (en) 2011-01-28 2018-04-24 Quanterix Corporation Systems, devices, and methods for ultra-sensitive detection of molecules or particles
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WO2013074833A1 (en) * 2011-11-16 2013-05-23 The Board Of Trustees Of The Leland Stanford Junior University Capture probe and assay for analysis of fragmented nucleic acids
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EP2794928B1 (de) 2011-12-22 2019-02-20 President and Fellows of Harvard College Zusammensetzungen und verfahren zum nachweis von analyten
WO2014163886A1 (en) 2013-03-12 2014-10-09 President And Fellows Of Harvard College Method of generating a three-dimensional nucleic acid containing matrix
WO2013184754A2 (en) 2012-06-05 2013-12-12 President And Fellows Of Harvard College Spatial sequencing of nucleic acids using dna origami probes
MY197877A (en) 2013-06-04 2023-07-22 Harvard College Rna-guided transcriptional regulation
WO2016007839A1 (en) 2014-07-11 2016-01-14 President And Fellows Of Harvard College Methods for high-throughput labelling and detection of biological features in situ using microscopy
GB201413718D0 (en) 2014-08-01 2014-09-17 Olink Ab Method for selecting a target nucleic acid sequence
GB201413717D0 (en) 2014-08-01 2014-09-17 Olink Ab Method for selecting a target nucleic acid sequence
EP3371329B1 (de) 2015-11-03 2026-03-25 President and Fellows of Harvard College Verfahren und vorrichtung zur volumetrischen bildgebung einer dreidimensionalen nukleinsäurehaltigen matrix
CA3210120C (en) 2016-04-25 2024-04-09 President And Fellows Of Harvard College Hybridization chain reaction methods for in situ molecular detection
GB201614023D0 (en) 2016-08-16 2016-09-28 Olink Bioscience Ab Double-stranded circle probes
JP7239465B2 (ja) 2016-08-31 2023-03-14 プレジデント アンド フェローズ オブ ハーバード カレッジ 蛍光ｉｎ ｓｉｔｕ配列決定による検出のための核酸配列ライブラリの作製法
GB2569252A (en) 2016-08-31 2019-06-12 Harvard College Methods of combining the detection of biomolecules into a single assay using fluorescent in situ sequencing
WO2020028194A1 (en) 2018-07-30 2020-02-06 Readcoor, Inc. Methods and systems for sample processing or analysis
WO2020076976A1 (en) 2018-10-10 2020-04-16 Readcoor, Inc. Three-dimensional spatial molecular indexing
WO2021155063A1 (en) 2020-01-29 2021-08-05 Readcoor, Llc Compositions and methods for analyte detection
US20220049303A1 (en) 2020-08-17 2022-02-17 Readcoor, Llc Methods and systems for spatial mapping of genetic variants
EP4596714A1 (de) * 2024-02-05 2025-08-06 Leica Microsystems CMS GmbH Marker zur analyse einer biologischen probe

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995022623A1 (en) 1994-02-16 1995-08-24 Ulf Landegren Circularizing nucleic acid probe able to interlock with a target sequence through catenation
WO1997020948A1 (en) 1995-12-05 1997-06-12 Koch Joern Erland A cascade nucleic acid amplification reaction
US5866337A (en) * 1995-03-24 1999-02-02 The Trustees Of Columbia University In The City Of New York Method to detect mutations in a nucleic acid using a hybridization-ligation procedure
US5872105A (en) * 1991-03-27 1999-02-16 Research Corporation Technologies Inc. Single-stranded circular oligonucleotides useful for drug delivery
WO1999049079A1 (en) 1998-03-25 1999-09-30 Ulf Landegren Rolling circle replication of padlock probes
US6235502B1 (en) * 1998-09-18 2001-05-22 Molecular Staging Inc. Methods for selectively isolating DNA using rolling circle amplification
US6372424B1 (en) * 1995-08-30 2002-04-16 Third Wave Technologies, Inc Rapid detection and identification of pathogens
US6867001B2 (en) * 2001-09-25 2005-03-15 Aisin Cosmos R&D Co., Ltd. Method for processing a library using ligation inhibition

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6221603B1 (en) * 2000-02-04 2001-04-24 Molecular Dynamics, Inc. Rolling circle amplification assay for nucleic acid analysis
GB0101402D0 (en) * 2001-01-19 2001-03-07 Amersham Pharm Biotech Uk Ltd Dual fidelity erca detection systems

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5872105A (en) * 1991-03-27 1999-02-16 Research Corporation Technologies Inc. Single-stranded circular oligonucleotides useful for drug delivery
WO1995022623A1 (en) 1994-02-16 1995-08-24 Ulf Landegren Circularizing nucleic acid probe able to interlock with a target sequence through catenation
US5866337A (en) * 1995-03-24 1999-02-02 The Trustees Of Columbia University In The City Of New York Method to detect mutations in a nucleic acid using a hybridization-ligation procedure
US6372424B1 (en) * 1995-08-30 2002-04-16 Third Wave Technologies, Inc Rapid detection and identification of pathogens
WO1997020948A1 (en) 1995-12-05 1997-06-12 Koch Joern Erland A cascade nucleic acid amplification reaction
WO1999049079A1 (en) 1998-03-25 1999-09-30 Ulf Landegren Rolling circle replication of padlock probes
US6558928B1 (en) * 1998-03-25 2003-05-06 Ulf Landegren Rolling circle replication of padlock probes
US6235502B1 (en) * 1998-09-18 2001-05-22 Molecular Staging Inc. Methods for selectively isolating DNA using rolling circle amplification
US20010039039A1 (en) 1998-09-18 2001-11-08 Sherman Weissman Methods for selectively isolating DNA using rolling circle amplification
US20020076704A1 (en) * 1998-09-18 2002-06-20 Sherman Weissman Methods for selectively isolating DNA using rolling circle amplification
US6867001B2 (en) * 2001-09-25 2005-03-15 Aisin Cosmos R&D Co., Ltd. Method for processing a library using ligation inhibition

Non-Patent Citations (27)

* Cited by examiner, † Cited by third party
Title
Ahmadian et al., "Analysis of the p53 Tumor Suppressor Gene by Pyrosequencing", BioTechniques, vol. 28, No. 1, 140-147, 2000.
Baner et al., "Signal amplification of padlock probes by rolling circle replication", Nucleic Acids Research, vol. 26, No. 22, 5073-5078, 1998.
Bonnen et al., "Haplotypes at ATM Identify Coding-Sequence Variation and Indicate a Region of Extensive Linkage Disequilibrium", Am. J. Hum Genet., 67:1437-1451, 2000.
Chee et al, "Accessing genetic information with high-density DNA arrays," Science, 274:610-614 (1996).
Douglas et al., "Experimentally-derived haplotypes substantially increase the efficiency of linkage disequilibrium studies", Nature Genetics, vol. 28, 361-364, Aug. 2001.
Drysdale et al., "Complex promoter and coding region beta2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness", PNAS, vol. 97, No. 19, pp. 10483-10488, Sep. 12, 2000.
Drysdale et al., "Complex promoter and coding region β2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness", PNAS, vol. 97, No. 19, pp. 10483-10488, Sep. 12, 2000.
Griffin et al., "Direct genetic analysis of matrix-assisted laser desorportion/ionization mass spectrometry", Proc Natl. Acad. Sci. USA, vol. 96, pp. 6301-6306, May 1999.
Heid et al., "Real Time Quantitative PCR", Genome Research, 6, 1054-9803/96, 1996.
Jin et al, "In situ hybridization: methods and applications," Journal of Clinical Laboratory Analysis, 11:2-9 (1997).
Kim, et al., "Structural Requirements for FOKI-DNA Interaction and Oligodeoxyribonucleotide-instructed Cleavage," J. Mol. Biol., 258, 638-649, 1996.
Kool, "Circular Oligonucleotides: New Concepts in Oligonucleotide Design", Annu. Rev. Biophys. Biomol. Struct., 25:1-28; 1996.
Landegren et al., "A Ligase-Mediated Gene Detection Technique", Science, vol. 241, 1077-1080, Aug. 26, 1988.
Liu et al., "Overlapping PCR for Bidirectional PCR Amplification of Specific Alleles: A Rapid One-Tube Method for Simultaneously Differentiating Homozygotes and Heterozygotes", Genome Research, 7:389-398, Cold Spring Harbor Laboratory Press, 1997.
Lyamichev et al, "Structure-specific endonucleolytic cleavage of nucleic acids by eubacterial DNA polymerases," Science, 260:778-783 (1993).
Lyamichev et al., "Polymorphism identification and quantitative detection of genomic DNA by invasive cleavage of oligonucleotide probes", Nature Biotechnology, vol. 17, 292-296, Mar. 1999.
Lyamichev et al., "Structure-Specific Endonuclease Cleavage of Nucleic Acids by Eubacterial DNA Polymerases," Science, vol. 260, May 7, 1993, pp. 778-783. *
Lyamichev et al., "Structure-Specific Endonucleolytic Cleavage of Nucleic Acids by Eubacterial DNA Polymerases", Science, vol. 260, 778-783, May 7, 1993.
Mashal et al., "Detection of mutations by cleavage of DNA heteroduplexes with bacteriophage resolvases," Nature Genetics, 9, 177-183 (1995).
Nilsson et al., "Padlock Probes: Circularizing Oligonucleotides for Localized DNA Detection", Science, vol. 265, 2085-2088, Sep. 30, 1994.
Nishigaki et al, "Type II restriction endonucleases cleave single-stranded DNAs in general," Nucleic Acids Research, 13(16):5747-5760 (1985).
Podhajska et al., "Conversion of the FokI endonuclease to a universal restriction enzyme: cleavage of phage M13mp7 DNA at predetermined sites", Gene, 40, 175-182, 1985.
Ronaghi et al., "Real-Time DNA Sequencing Using Detection of Pyrophosphate Release", Analytical Biochemistry, 242, 84-89, Article No. 0432, 1996.
Schena et al, "Quantitative monitoring of gene expression patterns with a complementary DNA microarray," Science, 270:467-470 (1995).
Stephens et al., "Haplotype Variation and Linkage Disequilibrium in 313 Human Genes", Science, vol. 293, 489-493, Jul. 2001.
Syvanen et al., "A Primer-Guided Nucleotide Incorporation Assay in the Genotyping of Apolipoprotein E", Genomics 8, 684-692 (1990).
Tyagi et al., "Molecular Beacons: Probes that Fluoresce upon Hybridization", Nature Biotechncology, vol. 14, 303-308, Mar. 1996.

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WO2013090469A1 (en) 2011-12-13 2013-06-20 Sequenta, Inc. Detection and measurement of tissue-infiltrating lymphocytes
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US9150905B2 (en) 2012-05-08 2015-10-06 Adaptive Biotechnologies Corporation Compositions and method for measuring and calibrating amplification bias in multiplexed PCR reactions
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US9279146B2 (en) 2012-12-21 2016-03-08 Roche Molecular Systems, Inc. Compounds and methods for the enrichment of mutated nucleic acid from a mixture
US11697840B2 (en) 2013-03-13 2023-07-11 Meso Scale Technologies, Llc. Method of detecting analyte in a sample with binding reagent, first detection reagent, and second detection reagent
US10114015B2 (en) 2013-03-13 2018-10-30 Meso Scale Technologies, Llc. Assay methods
US12163954B2 (en) 2013-03-13 2024-12-10 Meso Scale Technologies, Llc. Assay methods
US10908157B2 (en) 2013-03-13 2021-02-02 Meso Scale Technologies, Llc. Assay methods
US9618510B2 (en) 2013-03-13 2017-04-11 Meso Scale Technologies, Llc. Assay methods
US10077473B2 (en) 2013-07-01 2018-09-18 Adaptive Biotechnologies Corp. Method for genotyping clonotype profiles using sequence tags
WO2015002908A1 (en) 2013-07-01 2015-01-08 Sequenta, Inc. Large-scale biomolecular analysis with sequence tags
EP3486327A1 (de) 2013-07-01 2019-05-22 Adaptive Biotechnologies Corporation Grossflächige biomolekulare analyse mit sequenz-tags
US10526650B2 (en) 2013-07-01 2020-01-07 Adaptive Biotechnologies Corporation Method for genotyping clonotype profiles using sequence tags
US9708657B2 (en) 2013-07-01 2017-07-18 Adaptive Biotechnologies Corp. Method for generating clonotype profiles using sequence tags
US9518290B2 (en) 2013-09-10 2016-12-13 Samsung Electronics Co., Ltd. Method for detecting nucleic acids by amplification of a circularized nucleic acid
US9873908B2 (en) 2013-11-27 2018-01-23 Roche Molecular Systems, Inc. Methods for the enrichment of mutated nucleic acid from a mixture
US10227632B2 (en) 2013-11-29 2019-03-12 Q-Linea Ab Rolling circle amplification method
US11248253B2 (en) 2014-03-05 2022-02-15 Adaptive Biotechnologies Corporation Methods using randomer-containing synthetic molecules
US10435745B2 (en) 2014-04-01 2019-10-08 Adaptive Biotechnologies Corp. Determining antigen-specific T-cells
US10066265B2 (en) 2014-04-01 2018-09-04 Adaptive Biotechnologies Corp. Determining antigen-specific t-cells
US12351872B2 (en) 2014-04-01 2025-07-08 Adaptive Biotechnologies Corporation Determining antigen-specific T-cells
US11261490B2 (en) 2014-04-01 2022-03-01 Adaptive Biotechnologies Corporation Determining antigen-specific T-cells
US11338286B2 (en) 2014-04-14 2022-05-24 Q-Linea Ab Detection of microscopic objects
US10112194B2 (en) 2014-04-14 2018-10-30 Q-Linea Ab Detection of microscopic objects
US12411131B2 (en) 2014-05-15 2025-09-09 Meso Scale Technologies, Llc. Assay methods
US11525825B2 (en) 2014-05-15 2022-12-13 Meso Scale Technologies, Llc. Assay kits
US10392663B2 (en) 2014-10-29 2019-08-27 Adaptive Biotechnologies Corp. Highly-multiplexed simultaneous detection of nucleic acids encoding paired adaptive immune receptor heterodimers from a large number of samples
US10246701B2 (en) 2014-11-14 2019-04-02 Adaptive Biotechnologies Corp. Multiplexed digital quantitation of rearranged lymphoid receptors in a complex mixture
US11066705B2 (en) 2014-11-25 2021-07-20 Adaptive Biotechnologies Corporation Characterization of adaptive immune response to vaccination or infection using immune repertoire sequencing
US11047008B2 (en) 2015-02-24 2021-06-29 Adaptive Biotechnologies Corporation Methods for diagnosing infectious disease and determining HLA status using immune repertoire sequencing
US12428682B2 (en) 2015-02-24 2025-09-30 Adaptive Biotechnologies Corporation Methods for diagnosing infectious disease and determining HLA status using immune repertoire sequencing
US11041202B2 (en) 2015-04-01 2021-06-22 Adaptive Biotechnologies Corporation Method of identifying human compatible T cell receptors specific for an antigenic target
US10428325B1 (en) 2016-09-21 2019-10-01 Adaptive Biotechnologies Corporation Identification of antigen-specific B cell receptors
US12227796B2 (en) 2017-10-06 2025-02-18 10X Genomics, Inc. RNA templated ligation
US11597965B2 (en) 2017-10-06 2023-03-07 10X Genomics, Inc. RNA templated ligation
US11254980B1 (en) 2017-11-29 2022-02-22 Adaptive Biotechnologies Corporation Methods of profiling targeted polynucleotides while mitigating sequencing depth requirements
US12553887B2 (en) 2019-03-01 2026-02-17 Meso Scale Technologies, Llc. Electrochemiluminescent labeled probes for use in immunoassay methods, methods using such and kits comprising same
US12105084B2 (en) 2019-12-03 2024-10-01 Alamar Biosciences, Inc. Nucleic acid linked immune-sandwich assay (NULISA)
US12188929B2 (en) 2019-12-03 2025-01-07 Alamar Biosciences, Inc. Nucleic acid linked immune-sandwich assay (NULISA)
US12534751B1 (en) 2020-03-27 2026-01-27 Olink Proteomics Ab Products for protein analyte detection assays using antibodies
US12540355B1 (en) 2020-03-27 2026-02-03 Olink Proteomics Ab Nucleic acid reporter molecules for massively parallel DNA sequencing

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